P1200: ZILOVERTAMAB VEDOTIN (MK-2140) IN RELAPSED OR REFRACTORY (R/R) NON-HODGKIN LYMPHOMA (NHL): UPDATED RESULTS FROM THE PHASE 1 WAVELINE-001 STUDY
Authors: Stephen Spurgeon, Matthew Mei, Paul M. Barr, Jacqueline Barrientos, Sven de Vos, Richard Furman, Krish Patel, Philip Thompson, Michael Y. Choi, Avyakta Kallam, Siruo Wang, Uzor Ogbu, Patricia Marinello, Michael Wang
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: ROR1 is a transmembrane protein that is absent in mature tissues but highly expressed in certain hematologic malignancies, making it an attractive therapeutic target. Zilovertamab vedotin (ZV) is a ROR1-targeting antibody-drug conjugate that is being investigated in R/R hematologic malignancies in the phase 1 waveLINE-001 study (NCT03833180). Initial results showed ZV had a tolerable safety profile and promising antitumor activity in patients (pts) with R/R NHL (Wang ML et al. NEJM Evid. 2021;1[1]). Aims: To present updated results of waveLINE-001, including outcomes for pts with mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and Richter transformation (RT). Methods: Pts were ≥18 y old; had a histologic diagnosis of NHL (including MCL, follicular lymphoma [FL], marginal zone lymphoma [MZL], DLBCL, RT, Burkitt lymphoma, and T-cell NHL), chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia, acute lymphocytic leukemia, or acute myeloid leukemia (AML) that progressed during or relapsed after prior systemic therapy; and an ECOG PS of 0-2. 3 dosing schedules are being investigated in waveLINE-001; data from schedule 1 are presented. Pts received ZV IV at a starting dose of 0.5 mg/kg on day 1 Q3W, increasing to 2.5 mg/kg using an accelerated 3 + 3 dose-escalation design. The primary end point was the maximum tolerated dose and/or the recommended dosing regimen (RDR). Secondary end points included safety, ORR, DOR, PFS, and OS. Results: At the data cutoff (September 1, 2022), 56 pts had been enrolled in schedule 1, of whom 30 received ZV at the previously established RDR of 2.5 mg/kg. Median follow-up was 14.3 mo (range, 0.5-41.3). Median age was 70.0 y, 59% of pts were male, 48% had an ECOG PS of 0, 66% had received ≥3 prior therapies, 80% had NHL (3 had FL, 17 DLBCL, 17 MCL, 1 MZL, 7 RT), and 20% had other disease (3 AML, 7 CLL/SLL, 1 mixed histology). 13 pts with NHL (11 DLBCL, 2 RT) had undergone prior CAR-T/CAR-NK therapy. Any-cause AEs occurred in 54 pts (96%). Treatment-related AEs occurred in 41 pts (73%). Grade 3/4 treatment-related AEs occurred in 27 pts (48%), most commonly neutrophil count decreased (32%), platelet count decreased (11%), and peripheral neuropathy (7%). No pts died because of a treatment-related AE. Peripheral neuropathy occurred in 27 pts (48%); median time to onset was 15.6 weeks. No infusion-related reactions or tumor lysis syndrome were reported. Any-cause AEs led to discontinuation of ZV in 12 pts (21%) and interruption or reduction in 25 (45%). The ORR in all pts was 32% (95% CI, 20-46; 6 CR/12 PR). ORR was 29% (95% CI, 10.3-56.0; 3 CR/2 PR) in pts with DLBCL, 53% (95% CI, 28-77; 2 CR/7 PR) in MCL, and 57% (95% CI, 18-90; 1 CR/3 PR) in RT; no responses were reported in the other indications. Median DOR (range) was 4.6 mo (2.9-21.5) for pts with DLBCL, 10.0 (0.0-20.3) for MCL, and 2.8 (0.0-2.8) for RT. Median PFS (95% CI) was 4.5 mo (0.7-7.5) for DLBCL, 11.4 (4.0-NR) for MCL, and 4.7 (0.7-NR) for RT. Median OS (95% CI) was 9.1 mo (2.7-NR) for DLBCL, 18.0 (7.1-NR) for MCL, and 24.0 (2.7-NE) for RT. The ORR among pts with NHL who had undergone prior CAR-T/CAR-NK therapy was 31% (95% CI, 9-61; 2 CR/2 PR). Summary/Conclusion: The results of this updated analysis support prior findings from waveLINE-001 showing ZV had a tolerable safety profile and promising antitumor activity in pts with heavily pretreated DLBCL, MCL, and RT, including those who had received prior CAR-T/CAR-NK therapy. Keywords: Diffuse large B cell lymphoma, Mantle cell lymphoma, Clinical trial